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Targets for treating tumors

A technology for tumor treatment and targeting, which is applied in the field of tumor and chemotherapy, and can solve problems that have not been studied

Inactive Publication Date: 2016-04-20
天津药和生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Some of these are still hypothetical genes, meaning they haven't been studied

Method used

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Examples

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Effect test

example 1

[0229] Example 1 Synergistic inhibition of NF-κB activity

[0230] Overview: Typically, in vitro NF-κB activity is measured by artificial reporter gene assays, electronic gel retardation assays, and more recently DNA binding and ELISA methods. However, these methods all employ exogenous DNA oligonucleotides or constructs to measure DNA-binding transcriptional activity of specific NF-κB consensus and NF-κB promoter sequences. Furthermore, the NF-κB promoter function is different from the true promoter sequence. Real promoters require complex interactions between multiple protein molecules, while artificial NF-κB promoters may introduce artificial effects.

[0231] Experimental method: UM-SCC6 cells were transfected with effectene (Qiagen) 1) 20% dominant negative IKK1-KA (K44A) and 80% pUC19, 2) 20% dominant negative IKK2-KA (K44A ) and 80% pUC19 plasmid transfection, 3) 20% dominant negative IKK1-KA (K44A), 20% dominant negative IKK2-KA (K44A) and 60% pUC19, 4) 20% pcDNA3 an...

example 2

[0233] Example 2 Simultaneous inhibition of IKK1 and IKK2 can also lead to cancer cell death

[0234] In addition to inhibiting the activity of NF-κB, simultaneous transfection of SCC-6 cells with K44A-IKK1 and K44A-IKK2 also resulted in cell death ( figure 2 ). 48 hours after simultaneous transfection of K44A-IKK1andK44A-IKK2, the number of cells decreased by 85% ( figure 2 WST–1nono) and massive cell death ( figure 2 b). The data represent the average of 7 parallel experiments.

[0235] This result suggests that inhibition of NF-κB activity and resulting cancer cell death can only be achieved by simultaneously inhibiting both IKK1 and IKK2. In addition, co-transfected K44A-IKK1 and K44A-IKK2sensitize also enhanced the sensitivity of UM-SCC-6 cells to cisplatin and 5-FU by 10 to 100 times.

[0236] Example 2 Tetrazolium dye WST-1r increases cancer cell death caused by double inhibition of IKKs.

[0237] In this study, the conventional WST-1r method could not accurate...

example 4

[0241] Example 4 WST-1 promotes the death of HT1080 human sarcoma cells induced by three combination treatments.

[0242]Methods: HT1080 cells were cultured in 96-well plates and transfected with pUC19, pCDNA3, IKK1-KA, IKK1-KA+PUC19, and pCDNA3+pUC19 DNA plasmids, and then sequentially applied IKK inhibitor and WST-1r. Except for the control group, each group of cells was transfected with one of the above-listed plasmids for 24 hours, and then applied 3-30 MIKK inhibitor III, 24 hours later, and then applied WST for 4 hours, and then continued to culture overnight and then carried out with CCK8 kit Measured and measured 24, 48 and 96 hours thereafter.

[0243] The data showed that (1) tumor cells were transfected with DNA and applied IKK inhibitor III, and treated with WST-1r 24, 48 and 96 hours after treatment, all exhibited IKK inhibitor III dose-dependent cell growth inhibition and reduced cell survive. However, there was no significant difference between transfection pU...

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Abstract

The invention provides targets for treating tumors, wherein the biomolecules of the targets are selected from polynucleotide molecules and peptide molecules, the targets comprise polynucleotide sequences, protein, polypeptide molecules or genomes corresponding to short fragments of DNA sequences capable of being mapped to of the human genomes in the pUC19DNA sequence. The corresponding encoded molecules can become the targets for improving the treatment effects of cancers, and the potential medicines comprise but are not limited to siRNA, small-molecule inhibitors, polypeptide inhibitors, anti-sense RNA, anti-sense oligodeoxynucleotide, antibodies, antibody fragments, protein, and carrier dominant negative-sum interferons of DNA. The targets for treating tumors can be used for developing novel cancer treatment medicines, the functions of the chemotherapy medicines are improved, and the curative effects of the anti-cancer medicines can be enhanced in a synergism manner. The toxic and side effects of the chemotherapy medicines are greatly reduced, and a novel development path is provided for effective treatment on the cancers with no or low cytotoxicity.

Description

[0001] The present invention is a divisional application. This application is a divisional application with the filing date of 2008-07-02 and the application number of 200880023062.7, and the invention name is the formula, method and target for tumor treatment. [0002] Government Interests: [0003] This research was initiated in part at the NIH. The US Government may have certain rights in the inventions of this application. Technical field: [0004] The invention relates to the fields of tumor and chemotherapy. Specifically, the invention provides new medical applications, pharmaceutical ingredients, and targets for drug development to achieve more effective, non-toxic cancer treatments. Background technique [0005] Until now, chemotherapy and radiation therapy are still the main methods of treating cancer. These treatments aim to kill proliferating cells, not cancer cells. Therefore, these therapeutic methods have serious and potentially fatal side effects on the p...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K31/713A61K39/395A61K45/06A61P35/00
Inventor 于明
Owner 天津药和生物医药科技有限公司
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